This competing application seeks to extend, for a further 5 years, the consortium on Interplay of Genes and Environment across Multiple Studies. During the first funding cycle, we established a new collaboration among 8 existing longitudinal twin studies in the U.S., Sweden, and Denmark, set the stage for including an additional 7 longitudinal twin studies from the U.S., Finland, and Australia, and laid the foundation for studying gene- environment interplay in middle and older age through harmonization of these data sets. The aim was to understand how social factors across the lifespan are associated with physical (subjective health, chronic medical illness co-morbidity, functional ability), psychologicl and cognitive health outcomes, particularly in later life. Building on our preliminary results, the proposed work for the next funding cycle focuses on health disparities in aging, in particular, disparities related to socioeconomic status and sex. Health disparities, which have been targeted by Healthy People 2020 as a public health priority, present as paradoxes. SES disparities in aging outcomes, rather than being diminished, have actually been amplified even in modern welfare states with relatively low levels of income inequality and high levels of access to health care. Sex disparities are illustrated by men's shorter lifespans typified by a higher prevalence of acute conditions and women's longer lifespans characterized by a greater chronic disease burden, including higher prevalence of dementia. Through use of the twin design, we propose to identify contextual and individual environmental sources of disparities (differences in exposures and behaviors) and identify how these work in combination with genetic influences (differences in vulnerability). For example, what behaviors and exposures mediate SES disparities? Does high SES buffer genetic influences on health outcomes? Is women's higher rate of disorder due to more years to accumulate adverse exposures, differences in amount of exposure, sex differences in physiological vulnerability to the disorder, or differential genetic o physiological vulnerability to specific exposures compared to men? The answers have implications for how to intervene to reduce disease burden. To evaluate these explanations, we will use co-twin control/within pair models, biometric moderation models, biometric sex limitation models, and polygenic risk scores from genotyping completed during the first funding cycle. Across the 15 twin studies, there are nearly 52,000 individual twins. Within this sample are over 6900 identical twin pairs for within pair difference models, and over 12,500 dizygotic twin pairs including nearly 4000 opposite sex pairs, allowing for testing of hypotheses about sex-specific genetic and environmental influences. The consortium thus uniquely has the sample sizes necessary for the proposed research agenda.